Evaluation of anti-tumour properties of two depsidones - Unguinol and Aspergillusidone D - in triple-negative MDA-MB-231 breast tumour cells.

There is an ongoing search for new compounds to lower the mortality and recurrence of breast cancer, especially triple-negative breast cancer. Naturally occurring depsidones, extracted from the fungus Aspergillus, are known for their wide range of biological activities such as cytotoxicity, aromatase inhibition, radical scavenging, and antioxidant properties. Research showed the potential of depsidones as a treatment option for hormone receptor-positive breast cancer treatment, yet its effects on hormone receptor-negative breast cancer are still unkown. This study, therefore, investigated the potential of two depsidones (Unguinol and Aspergillusidone D) to induce apoptosis, cell cycle arrest and cytotoxicity, and reduce cell proliferation in the triple-negative MDA-MB-231 breast cancer cell line. Results were compared with the effects of the cytostatic drug doxorubicin, antimitotic agent colchicine and endogenous hormones 17ß-estradiol, testosterone and dihydrotestosterone. The cytostatic drugs and hormones affected the MDA-MB-231 cell line comparable to other studies, showing the usefulness of this model to study the effects of depsidones on a triple-negative breast cancer cell line. At sub µM levels, Unguinol and Aspergillusidone D did not influence cell proliferation, while cell viability was reduced at concentrations higher than 50 µM. Both depsidones induced apoptosis, albeit not statistically significantly. In addition, Unguinol induced cell cycle arrest in MDA-MB-231 cells at 100 µM. Our research shows the potential of two depsidones to reduce triple-negative breast cancer cell survival. Therefore, this group of compounds may be promising in the search for new cancer treatments, especially when looking at similar depsidones.

In silico study directed towards identification of the key structural features of GyrB inhibitors targeting MTB DNA gyrase: HQSAR, CoMSIA and molecular dynamics simulations.

Mycobacterium tuberculosis DNA gyrase subunit B (GyrB) has been identified as a promising target for rational drug design against fluoroquinolone drug-resistant tuberculosis. In this study, we attempted to identify the key structural feature for highly potent GyrB inhibitors through 2D-QSAR using HQSAR, 3D-QSAR using CoMSIA and molecular dynamics (MD) simulations approaches on a series of thiazole urea core derivatives. The best HQSAR and CoMSIA models based on IC50 and MIC displayed the structural basis required for good activity against both GyrB enzyme and mycobacterial cell. MD simulations and binding free energy analysis using MM-GBSA and waterswap calculations revealed that the urea core of inhibitors has the strongest interaction with Asp79 via hydrogen bond interactions. In addition, cation-pi interaction and hydrophobic interactions of the R2 substituent with Arg82 and Arg141 help to enhance the binding affinity in the GyrB ATPase binding site. Thus, the present study provides crucial structural features and a structural concept for rational design of novel DNA gyrase inhibitors with improved biological activities against both enzyme and mycobacterial cell, and with good pharmacokinetic properties and drug safety profiles.

Optimization of culture conditions for production of antimalarial menisporopsin A by the seed fungus Menisporopsis theobromae BCC 4162.

AIMS: The aim of this work was to optimize the production of a novel antimaralial menisporopsin A by the seed fungus Menisporopsis theobromae BCC 4162. METHODS AND RESULTS: Fungal cultures were grown in shake flasks at 25 degrees C in the basal medium with varying carbon and nitrogen sources, aeration rates and initial pH levels. The optimal carbon and nitrogen sources that improved the production of menisporopsin A were 1% fructose and 2.5% meat extract respectively. The production was further enhanced when the culture incubated on a shaker at 200 rev min(-1) with an initial pH of 8. The yield of menisporopsin A cultured under the optimized conditions was increased from 348.30 (obtained from basal medium) to 889.02 mg l(-1), and the cultivation time was reduced from 28 to only 4 days. As a result, the productivity of menisporopsin A was greatly enhanced to 222.26 mg l(-1) day(-1) which is 18-fold higher than that of basal conditions. Larger scale production in a fermenter was also achieved, yielding menisporopsin A at a maximal level of 594.32 mg l(-1) in 4 days. CONCLUSIONS: The optimized culture conditions for menisporopsin A production by M. theobromae BCC 4162 was the cultivation under shaking or agitation at 25 degrees C in fructose-meat extract medium with an initial pH of 8. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of menisporopsin A in a fermenter with a relatively short incubation period could be valuable for further utilization for chemical structure modification and derivatization.

Multiplolides A and B, new antifungal 10-membered lactones from Xylaria multiplex.

Two new 10-membered lactones, namely, multiplolides A (1) and B (2), were isolated from the broth extract of the fungus Xylaria multiplex BCC 1111. Chemical structures of 1 and 2 were elucidated on the basis of their spectral data. Multiplolides A (1) and B (2) exhibited antifungal activity against Candida albicans with IC(50) values of 7 and 2 microg/mL, respectively. Both 1 and 2 were inactive in the screening systems toward the malarial parasite Plasmodium falciparum (at 20 microg/mL) and were not cytotoxic to BC-1 and KB cell lines (at 20 microg/mL).

Antimalarial halorosellinic acid from the marine fungus Halorosellinia oceanica.

Three known compounds, 2-hexylidene-3-methylsuccinic acid (1), cytochalasin Q (2), and 5-carboxymellein (3), together with two new derivatives, 2-hexylidene-3-methylsuccinic acid 4-methyl ester (4) and an ophiobolane sesterterpene named halorosellinic acid (5), were isolated from culture broth of the marine fungus Halorosellinia oceanica BCC 5149. Compounds 1-3 exhibited moderate cytotoxicity against KB and BC-1 cell lines with IC(50) values of 1-13 microg/mL, while compounds 2, 3, 5, and 6 showed antimalarial activity with respective IC(50) values of 17, 4, 13, and 19 microg/mL. Halorosellinic acid (5) possessed only weak antimycobacterial activity with the minimum inhibitory concentration of 200 microg/mL.

A new antimycobacterial, 3 beta-acetoxy-15 alpha,22-dihydroxyhopane, from the insect pathogenic fungus Aschersonia tubulata.

Bioassay-guided fractionation of the cell extract of the insect pathogenic fungus Aschersonia tubulata BCC 1785 led to the isolation of dustanin (1), 3 beta,15 alpha,22-trihydroxyhopane (3), 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3 beta-ol (6), together with the new 3 beta-acetoxy-15 alpha,22-dihydroxyhopane (4). Chemical structures of these compounds were elucidated by spectral analyses as well as chemical transformation. Compounds 1 and 4 exhibited antimycobacterial activity with the minimum inhibitory concentration (MIC) of 12.5 micrograms/ml.

Potent antiviral potamogetonyde and potamogetonol, new furanoid labdane diterpenes from Potamogeton malaianus.

New furanoid labdane diterpenes, potamogetonyde (3) and potamogetonol (4), together with two known compounds, potamogetonin (1) and 15,16-epoxy-12-oxo-8(17),13(16),14-labdatrien-20,19-olide (2), were isolated from the CH(2)Cl(2) extract of Potamogeton malaianus. The chemical structures of 1-4 were elucidated by the analyses of their spectral data, mainly by 1D and 2D NMR techniques. Potamogetonyde (3) and potamogetonol (4) exhibited potent antiviral (HSV-1) activity with respective IC(50) values of 8 and 3 microg/mL. Compounds 1-4 possessed cytotoxicity toward insect cells (fall armyworm and mosquito larvae, IC(50) of 11-72 microg/mL). Furanoid diterpenes 3 and 4 also exhibited cytotoxicity against the Vero cell line with respective IC(50)'s of 31 and 28 microg/mL, while 1 and 2 were inactive at 50 microg/mL. Compounds 1-4 were inactive (at 20 microg/mL) against KB and BC cell lines and showed only weak antimycobacterial activity against Mycobacterium tuberculosis H37Ra with minimum inhibitory concentrations of 50-100 microg/mL.

Antimalarial preracemosols A and B, possible biogenetic precursors of racemosol from Bauhinia malabarica Roxb.

Racemosol and demethylracemosol, together with their possible biogenetic precursors, preracemosol A and preracemosol B, were isolated from the roots of Bauhinia malabarica Roxb. While only racemosol and demethylracemosol exhibited cytotoxicity against KB and BC cell lines, all four compounds exhibited moderate antimalarial activity.

New macrolactins from a marine Bacillus sp. Sc026.

Bioassay-guided fractionation of the EtOAc extract of a marine Bacillus sp. Sc026 culture broth has led to the isolation of the known compound, macrolactin F (1), together with two new compounds, 7-O-succinyl macrolactin F (2) and 7-O-succinyl macrolactin A (3). The chemical structures of 1-3 were elucidated on the basis of spectral data analyses and literature data comparison. Compounds 1-3 exhibited antibacterial activity against Bacillus subtilis and Staphylococcus aureus.

An antimalarial stilbene from Artocarpus integer.

Antimalarial activity-guided study of the aerial parts of Artocarpus integer led to the isolation of the prenylated stilbene, trans-4-(3-methyl-E-but-1-enyl)-3,5,2',4'-tetrahydroxystilbene with an EC50 of 1.7 micrograms/ml against Plasmodium falciparum in culture. The known stilbenes, trans-4-isopentenyl-3,5,2',4'-tetrahydroxystilbene and 4-methoxy-2,2-dimethyl-6-(2-(2,4-dihydroxy)phenyl-trans-ethenyl)chromene , were also isolated. Structures of these compounds were deduced on the basis of their spectral data.

Coumarins and carbazoles with antiplasmodial activity from Clausena harmandiana.

Activity guided fractionation of extracts from Clausena harmandiana have led to the identification of four known compounds, heptaphylline (1), clausine K (2), dentatin (5), and clausarin (6). All these compounds, except clausine K (2), exhibited antiplasmodial activity against Plasmodium falciparum. While the new dimethylated derivative 4, derived from 2, showed no antiplasmodial activity, the monomethylated product 3 (clausine H) exhibited activity comparable to that observed for compounds 1 and 5.

Antimycobacterial and antiplasmodial cyclodepsipeptides from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614.

Bioassay-guided fractionation of the crude extract from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614 led to the isolation and identification of two antimycobacterial and antiplasmodial cyclodepsipeptides, beauvericin and beauvericin A.

Fatty acid compositions in local sea cucumber, Stichopus chloronotus, for wound healing.

Fatty acid profile from crude extracts of local sea cucumber Stichopus chloronotus was determined using gas chromatography (GC) technique. The extracts were prepared separately in methanol, ethanol, phosphate buffer saline (PBS), and distilled water as part of our study to look at the affinity of these solvents in extracting the lipid from sea cucumber. The PBS and distilled water extractions indicate water-soluble components, while the organic fractions are extracted in methanol and ethanol as organic solvents. Furthermore, water extraction is the conventional method practiced in Malaysia. In our analysis the C14:0 (myristic), C16:0 (palmitic), C18:0 (stearic), C18:2 (linoleic), C20:0 (arachidic), and C20:5 (eicosapentaenoic, EPA) were significantly different (p < 0.01) in the four solvent extractions. However, the PBS extraction contained a much higher percentage of EPA (25.69%) compared to 18.89% in ethanol, 7.84% in distilled water, and only 5.83% in methanol, and variances were significantly different (p < 0.01 ). On the other hand, C22:6 (docosahexaenoic acid or DHA) is much higher in water extraction (57.55%), in comparison to the others where only 3.63% in PBS and 1.20% in methanol, and this difference is significant at p < 0.01. No DHA was detected in ethanol extractions. Subsequently, C18:1 (oleic acid) was only detected in PBS (21.98%) and water extraction (7.50%). It is interesting that palmitic acid, C16:() was higher in methanol (20.82%) and ethanol (2.18%), while 12.55% was detected in PBS and only 2.20% in water extraction: and again this was significantly different at p < 0.01. Although our results have shown that all four solvents were different in terms of their ability to extract fatty acids, the major component for tissue repair was well preserved. Probably this is one of the important precocious steps when working with a delicate sea cucumber, in both experimental and/or at the preparative stages. Freshness of the sea cucumber samples is important when undertaking this type of experiment. Finally, we believe that the local sea cucumber S. chloronotus contains all the fatty acids required to play a potential active role in tissue repair.

Norpregnane glycosides from a Thai soft coral, Scleronephthya pallida.

Two new norpregnane glycosides, 19-norpregna-1,3,5(10), 20-tetraen-3-O-alpha-fucopyranoside (3) and 19-norpregna-1,3,5(10), 20-tetraen-3-O-beta-arabinopyranoside (4), were isolated from the soft coral Scleronephthya pallida, along with two known steroids, pregna-1,20-dien-3-one (1) and 19-norpregna-1,3,5(10), 20-tetraen-3-ol (2). 19-Norpregna-1,3,5(10), 20-tetraen-3-O-alpha-fucopyranoside (3) exhibits moderate antimalarial and cytotoxic activities. The chemical structures of 1-4 were elucidated from spectroscopic data.

Fatty acid compositions in mucus and roe of Haruan, Channa striatus, for wound healing.

1. Fatty acid profiles in the external mucus extract and roe of Channa striatus were determined using gas chromatography (GC). 2. The mucus samples were collected by inducing hypothermic stress (-20 degrees C) for about 1 hr, and the roe were collected from gravid females at night soon after they liberated their eggs in a spawning program. 3. All mucus and roe samples were freeze-dried, except a part of roe which was not. 4. The mucus extract contained unsaturated fatty acid (oleic acid, C18:1 and linoleic acid, C18:2) as a major component, 21.25% and 22.47% of total lipid. 5. For the freeze- and nonfreeze-dried roe, the major components of fatty acid were somewhat similar to the mucus but with higher percentages: 58.56%, 26.08% and 45.76%, 20.94%. Interestingly, the nonfreeze-dried roe contained a large proportion of arachidic acid, C20:0 (22.16%), which was totally absent in the freeze-dried roe samples. 6. This profiling of the fatty acid mucus extract and roe is useful in strengthening the earlier claims that haruan possesses a potential remedy for wound healing (Mat Jais et al., 1994). Therefore, we are discussing the possibility of getting an optimum amount of the essential fatty acid for wound healing from various other parts of the fish without sacrificing the fish.